title: Neurogenic inflammation in an animal model of neuropathic pain.
abstract: Loose ligation of a rat sciatic nerve (chronic constriction injury (CCI) model) provokes signs and symptoms like those observed in reflex sympathetic dystrophy (RSD) patients. Primary afferent nociceptive C-fibers seem to be involved in an afferent orthodromic as well as in an efferent antidromic manner. In this study we hypothesize that consequent to development of antidromic impulses in C-nociceptive afferents, neuropeptides released from peripheral endings of these fibers, increase skin blood flow (SBF), vascular permeability, and tissue accumulation of polymorphonuclear leukocytes (PMNs). Collectively, these phenomena have been referred to as neurogenic inflammation. To investigate the presence of neurogenic inflammation in the CCI-model, we assessed skin blood flow (SBF) as well as the level of edema and accumulation of PMNs in muscle tissue obtained from the affected hindpaw. SBF was measured, by means of laser Doppler flowmetry, before ligation as well as at day 4 after ligation. At day 4, SBF measurements were performed before and after abolition of the capability of C-fibers to mediate a vasodilator response. To this end, capsaicin was applied perineurally. Increased vascular permeability was inferred from the level of edema of muscle tissue as determined by assessment of wet/dry weight ratios of muscle biopsies. PMN accumulation was investigated by enzymatic detection of myeloperoxidase (MPO) activity in muscle biopsies. Compared with preligation values, at day 4 SBF was increased more than twofold (p < 0.05). The latter response was annihilated by capsaicin application. Compared with sham operated controls, wet/dry ratios were higher in the ligated animals (1.104 vs. 1.068; p < 0.05). Likewise, when compared with sham operated controls, MPO activity was found to be increased in the ligated hindpaw (Optic Density 0.15 vs. 0.89; p < 0.001). In conclusion, the findings of this study indicate that loose ligation of a sciatic nerve induces an inflammatory response in the ipsilateral hindpaw, which most likely is mediated by release of neuropeptides from the peripheral endings of antidromically acting nociceptive C-fibres.
authors.affiliation: Department of General Surgery of the University Hospital Maastricht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Daemen
authors.forename: H A
authors.initials: HA
authors.lastname: Kurvers
authors.forename: P J
authors.initials: PJ
authors.lastname: Kitslaar
authors.forename: D W
authors.initials: DW
authors.lastname: Slaaf
authors.forename: P H
authors.initials: PH
authors.lastname: Bullens
authors.forename: F A
authors.initials: FA
authors.lastname: Van den Wildenberg
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D017078:Laser-Doppler Flowmetry; D008026:Ligation; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009443:Neuritis / Q000150:complications / Q000276:immunology / Q000473:pathology*; D009504:Neutrophils / Q000276:immunology; D009619:Nociceptors / Q000502:physiology*; D009929:Organ Size; D010146:Pain / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012019:Reflex Sympathetic Dystrophy / Q000150:complications / Q000276:immunology / Q000473:pathology*; D012584:Sciatic Nerve / Q000473:pathology; D012867:Skin / Q000098:blood supply
chemical_list: D009195:Peroxidase